title: Lactate dehydrogenase 5 expression in Non-Hodgkin lymphoma is associated with the induced hypoxia regulated protein and poor prognosis.
abstract: Lactate dehydrogenase 5 (LDH-5) is one of the major isoenzymes catalyzing the biochemical process of pyruvate to lactate. The purpose of this study was to investigate the expression of serum LDH-5 and test whether this enzyme is regulated by tumor hypoxia and represents a prognostic marker in patients with Non-Hodgkin's lymphoma (NHL). In this study, LDH-5 levels were detected using agarose gel electrophoresis in NHL patients (n = 266) and non-NHL controls including benign lymphadenectasis (n = 30) and healthy cohorts (n = 233). We also explored the expression of LDH-5 and hypoxia-inducible factor (HIF) 1α in NHL and benign controls by immunohistochemistry and immunofluorescence staining, respectively. Moreover, the role of LDH-5 in the progression of NHL was assessed by multivariate Cox analyses and Kaplan-Meier survival estimates. Serum concentrations of LDH-5 were significantly higher in NHL patients (9.3%) than in benign patients and healthy controls (7.5% and 7.2%, respectively, P<0.01). Application of LDH-5 detection increased the sensitivity of NHL detection, identifying 53.4% of NHL patients as positive, compared with the measurement of total LDH levels (36.5% sensitivity). LDH-5 concentrations increased with clinical stage, extra-nodal site involvement, and WHO performance status of patients with NHL. Exposure to a hypoxic environment induced the expression of LDH-5 and its overexpression correlated with HIF1α cytoplasmic accumulation in NHL cells. In multivariate analyses, LDH-5 was an independent marker for progression-free survival in patients with NHL (P<0.001). Overall, the expression of LDH-5 was elevated in NHL, showing an association with tumor hypoxia and unfavorable prognosis. Thus, LDH-5 emerges as a promising prognostic predictor for NHL patients.
authors.affiliation: Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, China ; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Renquan
authors.initials: R
authors.lastname: Lu
authors.forename: Minglei
authors.initials: M
authors.lastname: Jiang
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Chen
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xu
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Hu
authors.forename: Xinmin
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000097:blood / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D055815:Young Adult
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5